Assay reader operable to scan a test strip

ABSTRACT

Low-cost assay test strip readers are disclosed. Such readers enable creation of profiles of analyte reactions detected on an assay test strip utilizing a simple detector fixedly mounted to a body of the reader. The detector may be a single detector, such as a photodetector, which detects an optical signal at a single point. The assay test strip is inserted and/or removed from the test strip reader and the detector detects the optical elements of the strip during such insertion and/or removal. The movement of the test strip with respect to the body enables the detector to scan a length of the test strip, such that a one-dimensional profile of the optical signals can be generated. The reader may convert the detected profile into a displayable indication of analyte concentrations for diagnostic purposes. Moving the test strip relative to an array of detectors enables creation of a two-dimensional profile.

BACKGROUND

The present application is a continuation of U.S. patent applicationSer. No. 16/413,024, filed on May 15, 2019, entitled “ASSAY READEROPERABLE TO SCAN A TEST STRIP,” which is a continuation of U.S. patentapplication Ser. No. 12/774,138, filed on May 5, 2010, entitled “ASSAYREADER OPERABLE TO SCAN A TEST STRIP,” both of which are herebyincorporated by reference herein in their entirety.

BACKGROUND

Assay test kits are currently available for testing a wide variety ofmedical and environmental conditions or compounds, such as for testingfor the existence of a hormone, a metabolite, a toxin, or apathogen-derived antigen. Most commonly these tests are used to enablemedical diagnostics in the home testing context, the point of caretesting context, or the laboratory context. For example, lateral flowtests rely on a form of immunoassay in which the test sample flows alonga solid substrate via capillary action. Some tests are designed to makea quantitative determination, but in many circumstances the tests aredesigned to return or indicate a positive/negative qualitativeindication. Examples of assays which enable such qualitative analysisinclude blood typing, most types of urinalysis, pregnancy tests, andAIDS tests. For these tests, with proper illumination, a visuallyobservable indicator such as the presence of agglutination or a colorchange may indicate the result of the test.

Such assay-based tests can generally be divided into two categories. Afirst category includes assay-based tests in which, after the testsample flows along the solid substrate as noted above, the results ofthe tests (such as the colored or visible lines resulting from the test)are displayed or made visible to a human interpreter of the test. Forexample, a home pregnancy test may display one or more lines, whereinthe perception by the human interpreter of a designated quantity oflines (such as two lines) indicates a positive outcome of the test(e.g., that the person taking the test is pregnant). Such tests can beinexpensive, but can also result in operator error or uncertainty by thehuman interpreter of the tests.

A second category of assay-based tests are tests which can be read byone or more opto-electronic assay readers. In such situations, aconventional assay strip-based test is read and/or analyzed by one ormore opto-electronic devices. Such opto-electronic devices may utilizean optical detection technique to determine the concentration ofparticular analytes on the assay strip. These opto-electronic readerscan vary in terms of the technology utilized to detect the results ofthe test. Generally, however, these opto-electronic devices are moreexpensive than their human-interpretable counterparts.

A first type of opto-electronic reader can include imaging-basedopto-electronic readers. In such imaging-based readers, an array ofdetectors, such as a camera or other image detector, captures an imageof a two-dimensional portion of the assay strip. For example, an imagedetector may include a CMOS or CCD image sensor which includes at leastone semiconductor having a plurality of circuits that convert detectedlight to voltages. In such image sensors, circuitry on a silicon chipconverts the voltages indicative of detected light into digital datarepresentative of the sensed image. The device then applies known imageprocessing algorithms to the captured image to accommodate certainimaging artifacts, such as mechanical tolerance artifacts or spatialnon-uniformity artifacts. After the algorithms are applied, thecircuitry analyzes the sensed image and outputs data indicative of aresult. Such devices can also be modified to perform multiplexed tests,wherein a plurality of different portions of the assay strip areanalyzed in the same test, and a result is determined based on each ofthe analyzed portions of the strip.

Known imaging-based readers suffer from certain drawbacks. Specifically,the cost associated with the optical detector and the supportingelectronics required to analyze the image captured by the opticaldetector, such as a micro-controller with image processing capability,can be relatively high, and can prevent broad implementations of aconsumer-based product utilizing such opto-electronic readers.

A second type of opto-electronic reader can include photodiode basedopto-electronic readers. In such readers, one or more detectors of thereader is implemented as a photodiode, such as a PIN-diode, in which theamount of electricity flowing through the diode varies proportionatelyto the amount of optical signal detected, are used to collect dataindicative of a representation of the results of the test as indicatedvisually by the assay strip. Corresponding circuitry implements one ormore algorithms to analyze the amount of electricity flowing in thePIN-diode, and thus outputs or otherwise indicates the results of theassay test.

Photodiode-based readers also suffer from certain similar drawbacks tothose discussed above with respect to imagers. While the circuitryrequired to drive known photodiode-based readers may be simpler than thecircuitry required to drive similar imagers, and such readers maytherefore be more cost effective than corresponding imagers, knownphotodiode-based readers suffer from drawbacks relating to their lack ofscalability. Particularly, photodiode-based readers do not providespatial information. For example, certain known PIN-based readers cannotdifferentiate between a plurality of visible lines on an assay strip.Other photodiode-based readers can differentiate between (and monitor) aplurality of different analyte regions on an assay strip only byincluding a plurality of immovable detectors in the form of a pluralityof photodiode-diodes, with one detector corresponding to eachpotentially detected line. The cost and logistical issues associatedwith incorporating a plurality of photodiode-diodes in a single readercan thus be disadvantageous. Moreover, an existing reader with aplurality of detectors, implemented as a plurality of photodiode-diodes,may be limited to only analyzing assay test strips that detect thepresence of certain types of analytes based on the static positions ofthe analyte regions, and thus based on the static positions of thedetectors.

One known photodiode-based reader is implemented as the Clearblue®digital pregnancy test kit, manufactured and sold by SPD Swiss PrecisionDiagnostic. In this embodiment, two separate detectors (specifically,two separate PIN-diode based detectors) are positioned adjacent to aposition associated with a control line and a test line, The qualitativeresult of the test (i.e., whether the provider of the sample for thetest is pregnant), is based on which of these lines are visiblefollowing applying biological fluid to the assay test strip. Thus, whilea plurality of lines of an assay test strip can be detected, the deviceis limited to tests which have analyte regions corresponding to thefixed positions of the photodiode detectors. Additional test linesrequire additional photodiode detectors, and thus are associated withadditional costs and require development of different reader components.

To overcome the limitations of known photodiode-based readersattributable to the inability of such readers to simultaneously monitora plurality of different portions of an assay test strip, certain knownreaders implement a single detector mounted on an electro-mechanicalscanning mechanism. During testing, the scanning mechanism moves thephotodiode of the reader across a stationary assay strip and provides aone-dimensional profile of that assay strip. Most high-end commercialsystems available today that utilize photodiode to monitor a pluralityof different analytes contained in a single assay strip rely on suchelectro-mechanical scanning technology, wherein the scanner is driven bya stepper motor or other appropriate type of motor. However, suchsystems also suffer from certain drawbacks relating to the scanningapparatus' reliance on the stepper-motor. Such systems can be large,making portability difficult, and can be expensive, with costs rangingfrom two-thousand dollars to three-thousand dollars and upward.

Thus, it is desirable to create a portable, low-cost, stand-alone assaytest strip reader which utilizes a single detector (or array ofdetectors) to detect the presence of a plurality of different analyteregions on the assay test strip without regard for the pattern of theanalyte regions on the assay test strip.

SUMMARY

The present disclosure relates to an assay reader device that is capableof scanning for the presence of a plurality of lines at a plurality ofanalyte regions along the length of an assay test strip using at leastone detector fixedly connected to a body of the assay reader, such thatan assay test strip being examined moves relative to the at least onedetector. By affixing one or more detectors to the body of the reader,and by thereafter relying on the relative motion between the assay teststrip (such as during insertion and/or removal) and the body of thereader without an electro-mechanical scanning mechanism, the disclosedreader can utilize fixed detectors to scan a one- or two-dimensionalportion of the assay test strip. Thus, the disclosed assay test readerdoes not rely on an electro-mechanical powered or motorized scanningmechanism, such as an expensive scanning mechanism driven by steppermotors or other robotics, to scan the assay test strip by moving the oneor more detectors.

In various embodiments, the reader disclosed herein is discussed asincluding a sensor, such as a PIN-detector, which relies on a PIN-diodeto determine the presence or absence of color on an assay test strip. Itshould be appreciated that this discussion of a sensor, implemented as aPIN-diode based detector, is provided as indicative of the features ofan exemplary embodiment of the disclosed reader. That is, the disclosedreader is configured to utilize any appropriate type of detector todetect the presence or absence of a designated region on an assay teststrip. For example, the disclosed reader may include any suitable typeof photodetector capable of detecting the presence or absence of light,or other physically detectable electromagnetic properties including,magnetic field, polarization, wavelength, and radioactive emission. Sucha photodetector could be a sensor such as a PIN-diode, a CCD sensor, aCMOS sensor, an InGaAs sensor, or any other suitable type of sensorwhich can measure the presence or absence of light and/or color.Further, the detector disclosed herein may rely on a single sensorelement, such as a single PIN-diode, or may rely on an array of sensorelements, such as an array of PIN-diodes, to analyze the results of anassay test strip-based test. It should be appreciated that thediscussion of specific embodiments of sensor herein does not limit thescope of the disclosed reader and is merely exemplary.

In one embodiment, the detector utilized by the disclosed readergenerates a current proportional to the detected light and/or color onan assay test strip. For example, the detector may be a photodetectorsuch as those described above, and may be configured to generate acurrent based on detected photons. In another embodiment, the disclosedsensor generates current proportional to an amount of anothercharacteristic of the disclosed assay test strip. For example, thedisclosed detector may generate current proportional to an amount of amagnetic field generated by an assay test strip. The detector utilizedin the disclosed reader may detect the presence of other characteristicsas appropriate depending on the type of assay test strip utilized andthe mechanism by which the results of the test are determined.

The disclosed assay reader may additionally include control electronicsto process the data resulting from scanning the test strip. For example,the control electronics may convert raw signal data generated duringmovement of the assay test strip with respect to the body of the assayreader into a profile of the assay test strip. The profile may indicatethe presence or absence of certain analytes in a biological or chemicalsolution to which the assay test strip was exposed.

Further, in one embodiment the disclosed reader is discussed as beingconfigured to receive an assay test strip and to determine one or morecharacteristics of that strip. It should be appreciated that as usedherein, the term “assay test strip” or “assay strip” may refer to eitheran assay strip without any housing and/or casing, and/or may refer to anassay test strip which includes a portion on which the sample isdisposed, contained within a housing or casing, such that the assay testtrip is in fact an assembly or a cartridge in which the assay-basedreactions occur. In one embodiment, wherein the assay test strip is notenclosed within a housing, the strip itself is inserted in the body ofthe reader, and the sensors disposed in the reader sense the presence orabsence of appropriate characteristics of the strip itself. In anotherembodiment, wherein the assay test strip is disposed within a housing toform a cartridge, the assay test strip cartridge is inserted into thebody of the disclosed reader, and the results of the test are determinedby passing the detector(s) in the proximity of the reacting portion ofthe assay test strip. Thus, as they are used herein, the terms “assaytest strip” and/or “assay strip” should not be limited in itsinterpretation to test strips without a housing. It should be understoodthat such terms can encompass cartridges in which an assay test stripsubstrate is enclosed within a housing, casing, or other enclosingelement to form a cartridge which is inserted in the body of thedisclosed reader.

In one embodiment, the disclosed reader also includes a displayconfigured to output an indication of an outcome of a test. For example,the disclosed reader may include a display device configured to displaydata indicative of a qualitative outcome of a test, such as a “positive”or “negative” outcome determined by the control electronics connected tothe at least one detector. The control electronics may determine thisqualitative outcome based on the detected profile of the assay teststrip, such that human error in interpreting visual characteristics ofan assay test strip following exposure of the test strip to a biologicalor chemical fluid is reduced or eliminated. Alternatively or inaddition, the disclosed reader may include at least one displayconfigured to output a quantitative indication of a test. Moreover, thedisclosed reader may include control electronics connected to thedisplay, which determine an indication of one or more signal strengthsdetermined by the detectors of the disclosed reader. In such anembodiment, the display device coupled to the detector via the controlelectronics may be configured to output an indication of a signalstrength detected by the detector, which indication may represent thequantitative outcome of a test.

The present disclosure relates to assay test strip readers that includea body sized to receive an assay strip, the assay strip usable toperform an analyte test, at least one detector positioned within thebody such that an inserting of the assay strip or a removing of theassay strip by an operator, which results in movement of the assay stripwith respect to the body and the at least one detector, causes the atleast one detector to detect a first signal based on a first point onthe assay strip and to detect a second signal based on a differentsecond point on the assay strip, and at least one signal converterelectronically connected to the at least one detector, the at least onesignal converter configured to receive the first signal and the secondsignal detected by the detector, generate at least one result signalindicative of a result of the analyte test based on the first opticalsignal and the second optical signal, and output the least one resultsignal.

In an embodiment, the body includes an assay strip receiving area sizedto receive the assay strip.

In an embodiment, the first signal is a first optical signal indicativeof an optical characteristic of the first point of the assay strip andwherein the second signal is a second optical signal indicative of theoptical characteristic of the second point of the assay strip. In afurther embodiment, the first optical signal is indicative of ameasurement of color at the first point of the assay strip and whereinthe second optical signal is indicative of a measurement of color at thesecond point of the assay strip.

In an embodiment, the assay test strip reader includes at least oneaudio/visual indicator affixed to the body and electronically connectedto the at least one signal converter, the at least one audio/visualindicator configured to output an audio/visual representation of the atleast one result signal. In a further embodiment, the analyte test is amedical diagnostic test, and wherein the audio/visual representation ofthe at least one result signal indicates a result of the medicaldiagnostic test. In an embodiment, the at least one result signalincludes a visual display of a qualitative result of the medicaldiagnostic test.

In an embodiment, at least one result signal includes a visual displayof a quantitative result of the medical diagnostic test based, at leaston part, on a first intensity of the first signal based on the firstpoint on the assay strip.

In an embodiment, the assay strip is slidably insertable in the bodysuch that inserting the assay strip includes the operator sliding theassay strip in a first direction with respect to the body and removingthe assay strip includes the operator sliding the assay strip in adifferent second direction with respect to the body.

In an embodiment, the at least one detector includes a photodiodedetector. In another embodiment, the at least one detector includes animager.

In an embodiment, the at least one result signal is indicative of aone-dimensional representation of an appearance of the assay strip.

In an embodiment, the at least one detector includes a plurality ofdetectors arranged as an array of detectors, and wherein the at leastone result signal includes a two-dimensional representation of anappearance of the assay strip.

In an embodiment, a position sensing mechanism is included to detect atleast one position of the assay test strip with respect to the reader.The position sensing mechanism can be based on an optical or anelectro-mechanical mechanism. Examples of an electro-mechanical positionsensing mechanism including a sliding or rotating potentiometer wherethe output signal is indicative of a relative position.

In an embodiment, the assay strip includes a test portion and an encoderportion, the test portion including at least one analyte reactionsection, the encoder portion including a plurality of visible markingsat a plurality of known positions, and wherein the at least one detectoris positioned to detect an encoder optical signal indicative of theposition of the assay strip within the body and to detect an analyteoptical signal indicative of a reaction of at least one analyte.

In an embodiment, the at least one signal converter is configured toreceive the encoder optical signal and to generate the at least oneresult signal based, at least in part, on the encoder optical signal.

In an embodiment, the encoder optical signal indicates an expectedposition of the at least one analyte reaction section on the assay stripand wherein the at least one result signal is based on whether at leastone line is displayed at the expected position of the at least oneanalyte reaction. In a further embodiment, the encoder optical signal isa bar code indicative of at least one characteristic of the analytetest.

In an embodiment, the assay test strip reader disclosed herein includesan assay test strip including a plurality of analyte reaction regions, abody, a spring mechanism including a release positioned within the bodysuch that after the spring mechanism is loaded, activation of therelease causes the spring mechanism to move the test strip outwardrelative to the body, at least one detector positioned within the bodysuch that upon moving the assay test strip outward relative to the body,the detector detects an optical characteristic of each of the pluralityof analyte reaction regions of the assay test strip, and at least onedisplay device configured to output an indication of a profile of theassay test strip, the profile based on the plurality of opticalcharacteristics associated with the plurality of analyte reactionregions of the assay test strip.

In an embodiment, the assay test strip is exposed to at least onebiological fluid prior to moving the assay test strip relative to thebody.

In an embodiment, the assay test strip is associated with a biologicaltest, and which includes control electronics coupled to the at least onedetector, the control electronics configured to generate the profile ofthe assay test strip, the profile indicative of a result of thebiological test.

In an embodiment, the control electronics enable a connection to aseparate processor-based device such that the profile of the assay teststrip can be stored on a memory device of the separate processor-baseddevice.

In an embodiment, the assay test strip reader includes at least onelight source associated with the at least one detector, the at least onelight source configured to illuminate at least one portion of the assaytest strip being scanned with the at least one detector.

In an embodiment, the assay test strip is encased in an assay test striphousing, and wherein the body includes an assay test strip housingreceiving portion sized to receive the assay test strip housing.

In an embodiment, an operator inserts the assay test strip in the bodyto load the spring mechanism, and wherein operator activates the releaseto move the test strip outward relative to the body.

In an embodiment, the at least one detector also detects the opticalcharacteristic of each of the plurality of analyte reaction regions ofthe assay test strip prior to loading the spring mechanism.

In an embodiment, the assay test strip reader includes controlelectronics coupled to the at least one detector, and wherein thecontrol electronics are configured to send a release signal to activatethe release to cause the spring mechanism to move the test strip outwardrelative to the body, the release signal indicative that the at leastone detector is ready to detect the optical characteristic of each ofthe plurality of analyte reaction regions of the assay test strip.

In an embodiment, insertion of the assay test trip causes the assay teststrip reader to power on, or to wake up from a sleep state or alow-power state.

A method of analyzing an assay test strip disclosed herein includesenabling an operator to move the assay test strip relative to a body ofan assay reader, the assay reader including at least one detectorfixedly connected to the body, detecting a presence of at least oneanalyte reaction region based on at least one optical characteristic ofthe at least one analyte reaction region during the operator-causedmoving of the assay test strip relative to the body of the assay reader,and outputting data indicative of the detected at least one opticalcharacteristic of the at least one analyte reaction region using anaudio/visual output device electrically connected to the at least onedetector.

In an embodiment, the at least one detector includes a photodiodedetector. In another embodiment, the at least one detector includes animager.

In an embodiment, enabling the operator to move the assay test striprelative to the body of the assay reader includes enabling the operatorto insert the assay test strip in the body of the assay reader, causingthe assay test strip to engage at least one spring mechanism, andenabling the operator to cause the spring mechanism to release.

In an embodiment, outputting the data indicative of the detected atleast one optical characteristic includes sending data to at least oneprocessor-based device separate from the assay reader.

In an embodiment, the data is sent to the at least one processor-baseddevice via a wired or wireless connection, such as a Bluetoothconnection, a WiFi connection, or a USB connection.

In an embodiment, the disclosed method includes determining a profile ofthe assay test strip according to the detected presence of the at leastone analyte reaction region.

In an embodiment, the at least one detector includes one assay detectorfixedly connected to the body of the assay reader, and wherein theprofile includes a one-dimensional profile of the assay test strip.

In an embodiment, the at least one detector includes a plurality ofassay detectors fixedly connected to the body of the assay reader in alinear arrangement perpendicular to a direction of motion of the assaytest strip, and wherein the profile includes a two-dimensional profileof the assay test strip.

Additional features and advantages are described herein, and will beapparent from, the following Detailed Description.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a schematic diagram of an example assay readercontaining three test lines as disclosed herein, including a singledetector, without illustrating the body of the reader.

FIG. 2 illustrates a plan view of a device implementing an examplesingle-detector assay reader as disclosed herein.

FIG. 3 illustrates a 2-dimensional (2D) image representing an assaystrip having two test lines, where the x and y positions of the 2D imagecorrespond to positions on the assay strip, and where the signalstrength is represented by the intensity of the x and y location.

FIG. 4 illustrates a 1-dimensional (1D) profile of an assay strip havingtwo test lines, where the vertical axis represents the detected signalstrength and the horizontal axis represents the position of the assaystrip.

DETAILED DESCRIPTION

The present disclosure relates to low-cost, portable assay test stripreaders that are capable of detecting the presence of analytes in abiological sample using a plurality of spaced apart antibody regions onassay test strips. More particularly, the present disclosure relates tolow-cost assay test strip readers that can determine the presence orabsence of analyte reactions on assay test strips at a plurality ofdifferent locations on the assay test strips without requiring expensivescanning equipment and without requiring a separate detector to bealigned with each antibody region (and thus with each possible analytereaction) of the test strip.

Conventional assay test strip readers are limited either because adifferent detector must be associated with each potential position of avisually identifiable analyte reaction, or because a scanning apparatusmust use a complex, expensive, motor-driven scanner to scan a one- ortwo-dimensional portion of an assay test strip and to generate a one- ortwo-dimensional profile of that portion of the assay test strip. Suchconventional assay test strip readers are too costly to be realisticallyimplemented as robust home-use test kits.

The assay readers of the present disclosure represent improvements toknown assay readers because they are low-cost and are able to detect thepresence or absence of analyte reactions at a plurality of differentlocations on an assay test strip regardless of the number or positionsof the potential reactions. The disclosed assay readers may enable theseimproved functionalities by utilizing one or more detectors or sensorswhich are each fixedly connected to a body, and by relying on the motionof an assay test strip (such as the insertion or removal of the assaytest strip from the assay reader) with respect to both the body and thedetector or sensor (which are fixed with respect to one another) togenerate an analyte profile spanning a plurality of different regions orlocations on the assay test strip.

Referring now to FIG. 1, a schematic diagram of an embodiment of thedisclosed assay reader 100 is illustrated. It should be appreciated thatin the illustrated embodiment, a body portion of the assay reader (whichhouses the detector and the associated electronics, as illustrated inFIG. 2, discussed below) and the associated control electronics of theassay test reader are not illustrated for clarity. Thus, the illustratedschematic diagram 100 of the disclosed assay reader includes an assaystrip 102 and a detector 104.

The assay strip 102 includes a plurality of regions 106 a, 106 b, and106 c. In the illustrated embodiment, the regions 106 a, 106 b, and 106c each contain substances, such as antibodies, disposed on the assaystrip 102. The substances may react with analytes contained in abiological fluid, and may cause the regions 106 a, 106 b, and/or 106 cto change intensities or colors in the presence of a particular analyte.In the illustrated embodiments, depending upon the results of the testsperformed with the assay strip 102, one or more of the regions 106 a,106 b, and 106 c may not be visible following application of biologicalfluid to the assay strip 102 (e.g., if a tested-for analyte is notpresent in the biological sample applied to the assay strip 102). Itshould be further appreciated that in the illustrated embodiment, theassay strip 102 is not contained within a housing, casing, or othershell. That is, the illustrated assay strip 102 is inserted directlyinto the body of the disclosed reader, and is not provided as an assaystrip cartridge or other type of encased assay test strip. However, inother embodiments, not illustrated in FIG. 1, it should be appreciatedthat the assay test strip is enclosed or encased to form an assay teststrip cartridge.

The illustrated embodiment of the assay test reader 100 disclosed hereinalso includes a detector 104. As will be discussed in more detail below,the detector 104 may include a photodiode based detector, an imager, orany other appropriate type of detector. Further, the detector 104 mayinclude an optics 104 a to improve light collection efficiency of thedetector 104. For example, the optics 104 a may include an aperture,such as a slit-shaped aperture or a pin-hole aperture, to enhance thefocus and/or signal strength of the light on to the active portion ofthe detector. In various embodiments, the optics 104 a of the detector104 may be one or more lenses, mirrors, diffractive elements, orapertures, such as the pin-hole or slit-type aperture mentioned above,may be clear, colored, or coated material such as glass or plastic, ormay be any other suitable optical device for improving the lightcollection efficiency and capabilities of the detector 104.

The detector 104 illustrated in FIG. 1 is configured to determinewhether a line is present (i.e., whether an analyte present in thebiological sample has reacted with a substance, resulting in a visualindication of the reaction) at the portion 104 b of the assay strip 102directly under the detector 104. It should be appreciated that when thedetector 104 is in the illustrated position with respect to the assaytest strip 102, the detector 104 does not detect the presence of a line(such as the lines illustrated at regions 106 a, 106 b, or 106 c), asthe analyzed portion 104 b of the assay strip 102 does not include anappropriate substance to react with the biological sample.

The illustrated schematic representation of the assay reader 100includes arrow 108, which indicates the relative motion of the assaystrip 102 with respect to the detector 104. In the illustratedembodiment, the arrow 108 indicates that during use, the assay strip 102can be moved laterally with respect to the detector 104. It should beappreciated that given such movement, the detector 104 may at variouspoints during the movement of the assay strip 102 detect the presence oflines 106 a, 106 b, or 106 c. It should thus be appreciated that whenmovement of the assay strip 102 with respect to the body (not shown) andthe detector 104 of the assay reader 100 results in portion 104 b of theassay test strip 102 which is directly under the detector 104 coincidingwith one of the lines 106 a, 106 b, or 106 c, the detector may detectthe presence of one of the illustrated lines. The detection of thepresence of such a line, which is indicative of the presence of ananalyte, is thereafter usable to determine the results of a medicaldiagnostic test.

Upon detection of an appropriate visual indication of a reaction, suchas upon detection of a line at region 106 a, 106 b, or 106 c, thedisclosed assay reader sends a signal to associated control electronics(not shown) for processing. This control electronics may include analogprocessing, such as amplification and filtering, and/or digitalprocessing. The signal may be indicative of a profile of the assay teststrip 102, and may include information usable by the control electronicsto make a qualitative determination as to the outcome of a medical test.For example, the control electronics may determine that based on acertain pattern of detected lines, the person from whom biological fluidoriginated is or is not pregnant based on the presence or absence ofcertain analytes in the person's urine.

In an embodiment, the electronics include at least one display deviceconnected to the detector, such that a signal sent by the detectorresults in the display device displaying the determined qualitativeoutcome of the medical test to the user of the assay strip. For example,in an analyte test designed to determine whether a person is pregnant,if the determination is that the person is pregnant, the display devicemay display the word “pregnant.” Alternatively, the display device maydisplay an indication of a quantitative result of a test, such as anindication regarding the intensity of a line of an assay test strip.

Exemplary assays contemplated for use with the assay test readers of thepresent disclosure include lateral flow assay test strips. Lateral flowassay test strips may comprise a membrane system that forms a singlefluid flow pathway along the test strip. The membrane system may includeone or more components that act as a solid support for immunoreactions.For example, porous, bibulous or absorbent materials may be placed on astrip such that they partially overlap, or a single material can beused, in order to conduct liquid along the strip. The membrane materialsmay be supported on a backing, such as a plastic backing. In a preferredembodiment, the test strip includes a glass fiber pad, a nitrocellulosestrip and an absorbent cellulose paper strip supported on a plasticbacking.

Antibodies that react with the target analyte and/or a detectable labelsystem are immobilized on a solid support provided by the test strip.The antibodies may be bound to the test strip by adsorption, ionicbinding, van der Waals adsorption, electrostatic binding, or by covalentbinding, by using a coupling agent, such as glutaraldehyde. For example,the antibodies may be applied to the conjugate pad and nitrocellulosestrip using standard dispensing methods, such as a syringe pump, airbrush, ceramic piston pump or drop-on-demand dispenser. In a preferredembodiment, a volumetric ceramic piston pump dispenser may be used tostripe antibodies that bind the analyte of interest, including a labeledantibody conjugate, onto a glass fiber conjugate pad and anitrocellulose strip. The test strip may or may not be otherwisetreated, for example, with sugar to facilitate mobility along the teststrip or with water-soluble non-immune animal proteins, such asalbumins, including bovine (BSA), other animal proteins, water-solublepolyamino acids, or casein to block non-specific binding sites.

Any antibody, including polyclonal or monoclonal antibodies, or anyfragment thereof, such as the Fab fragment, that binds the analyte ofinterest, is contemplated for use herein.

An antibody conjugate containing a detectable label may be used to bindthe analyte of interest. The detectable label used in the antibodyconjugate may be any physical or chemical label capable of beingdetected on a solid support using a reader, preferably a reflectancereader, and capable of being used to distinguish the reagents to bedetected from other compounds and materials in the assay.

Suitable antibody labels are well known to those of skill in the art andinclude, but are not limited to, enzyme-substrate combinations thatproduce color upon reaction, colored particles, such as latex particles,colloidal metal or metal or carbon sol labels, fluorescent labels, andliposome or polymer sacs, which are detected due to aggregation of thelabel. In an embodiment, colloidal gold is used in the labeled antibodyconjugate. The label may be derivatized for linking antibodies, such asby attaching functional groups, such as carboxyl groups to the surfaceof a particle to permit covalent attachment of antibodies. Antibodiesmay be conjugated to the label using well known coupling methods.

The assay test strip may be any conventional lateral flow assay teststrip such as those disclosed in EP 291194 or U.S. Pat. No. 6,352,862.The test strip may comprise a porous carrier containing a particulatelabeled specific binding reagent and an unlabelled specific bindingreagent.

An assay, as discussed herein, may be configured to test for thepresence of one or more analytes in a biological sample applied to theassay. A sample may include, for example, anything which may contain ananalyte. The sample may be a biological sample, such as a biologicalfluid or a biological tissue. Examples of biological fluids includeurine, blood, plasma, serum, saliva, semen, stool, sputum, cerebralspinal fluid, tears, mucus, amniotic fluid or the like. Biologicaltissues are aggregate of cells, usually of a particular kind togetherwith their intercellular substance that form one of the structuralmaterials of a human, animal, plant, bacterial, fungal or viralstructure, including connective, epithelium, muscle and nerve tissues.Examples of biological tissues also include organs, tumors, lymph nodes,arteries and individual cell(s). A liquid sample may refer to a materialsuspected of containing the analyte(s) of interest, which material hassufficient fluidity to flow through an immunoassay device in accordanceherewith. The fluid sample can be used as obtained directly from thesource or following a pretreatment so as to modify its character. Suchsamples can include human, animal or man-made samples. The sample can beprepared in any convenient medium which does not interfere with theassay. Typically, the sample is an aqueous solution or biological fluidas described in more detail below.

A fluid sample (e.g., biological fluid) may refer to a materialsuspected of containing the analyte(s) of interest, which material hassufficient fluidity to flow through an immunoassay device in accordanceherewith. The fluid sample can be used as obtained directly from thesource or following a pretreatment so as to modify its character. Suchsamples can include human, animal or man-made samples. The sample can beprepared in any convenient medium which does not interfere with theassay.

The fluid sample can be derived from any source, such as a physiologicalfluid, including blood, serum, plasma, saliva, sputum, ocular lensfluid, sweat, urine, milk, ascites fluid, mucous, synovial fluid,peritoneal fluid, transdermal exudates, pharyngeal exudates,bronchoalveolar lavage, tracheal aspirations, cerebrospinal fluid,semen, cervical mucus, vaginal or urethral secretions, amniotic fluid,and the like. Herein, fluid homogenates of cellular tissues such as, forexample, hair, skin and nail scrapings, meat extracts and skins offruits and nuts are also considered biological fluids. Pretreatment mayinvolve preparing plasma from blood, diluting viscous fluids, and thelike. Methods of treatment can involve filtration, distillation,separation, concentration, inactivation of interfering components, andthe addition of reagents. Besides physiological fluids, other samplescan be used such as water, food products, soil extracts, and the likefor the performance of industrial, environmental, or food productionassays as well as diagnostic assays. In addition, a solid materialsuspected of containing the analyte can be used as the test sample onceit is modified to form a liquid medium or to release the analyte.

Exemplary lateral flow devices include those described in U.S. Pat. Nos.4,818,677, 4,943,522, 5,096,837 (RE35,306), 5,096,837, 5,118,428,5,118,630, 5,221,616, 5,223,220, 5,225,328, 5,415,994, 5,434,057,5,521,102, 5,536,646, 5,541,069, 5,686,315, 5,763,262, 5,766,961,5,770,460, 5,773,234, 5,786,220, 5,804,452, 5,814,455, 5939,331, and/or6,306,642.

An analyte can be any substance for which there exists a naturallyoccurring analyte specific binding member or for which ananalyte-specific binding member can be prepared. e.g., carbohydrate andlectin, hormone and receptor, complementary nucleic acids, and the like.Further, possible analytes include virtually any compound, composition,aggregation, or other substance which may be immunologically detected.That is, the analyte, or portion thereof, will be antigenic or haptenichaving at least one determinant site, or will be a member of a naturallyoccurring binding pair.

Analytes include, but are not limited to, toxins, organic compounds,proteins, peptides, microorganisms, bacteria, viruses, amino acids,nucleic acids, carbohydrates, hormones, steroids, vitamins, drugs(including those administered for therapeutic purposes as well as thoseadministered for illicit purposes), pollutants, pesticides, andmetabolites of or antibodies to any of the above substances. The termanalyte also includes any antigenic substances, haptens, antibodies,macromolecules, and combinations thereof (see, e.g., U.S. Pat. Nos.4,366,241; 4,299,916; 4,275,149; and 4,806,311).

In an embodiment, a sample receiving zone on the surface of a lateralflow assay test strip accepts a fluid sample that may contain one ormore analytes of interest. In an embodiment, the sample receiving zoneis dipped into a fluid sample. A label zone is located downstream of thesample receiving zone, and contains one or more mobile label reagentsthat recognize, or are capable of binding the analytes of interest.Further, one or more test regions may be disposed downstream from thelabel zone, and may contain one or more test and/or control zones. Thetest zone(s) generally contain means which permit the restraint of aparticular analyte of interest in each test zone. Frequently, the meansincluded in the test zone(s) comprise an immobilized capture reagentthat binds to the analyte of interest. Generally the immobilized capturereagent specifically binds to the analyte of interest. Thus, as thefluid sample flows along the matrix, the analyte of interest will firstbind with a mobilizable label reagent in the label zone, and then becomerestrained in the test zone.

In an embodiment, the sample receiving zone may be comprised of anabsorbent application pad. Suitable materials for manufacturingabsorbent application pads include, but are not limited to, hydrophilicpolyethylene materials or pads, acrylic fiber, glass fiber, filter paperor pads, desiccated paper, paper pulp, fabric, and the like. Forexample, the sample receiving zone may be comprised of a material suchas a nonwoven spunlaced acrylic fiber.

The sample receiving zone may be comprised of any material from whichthe fluid sample can pass to the label zone. Further, the absorbentapplication pad can be constructed to act as a filter for cellularcomponents, hormones, particulate, and other certain substances that mayoccur in the fluid sample. Application pad materials suitable for use bythe present disclosure also include those application pad materialsdisclosed in U.S. Pat. No. 5,075,078.

In a further embodiment, the sample receiving zone may be comprised ofan additional sample application member (e.g., a wick). Thus, in oneaspect, the sample receiving zone can comprise a sample application padas well as a sample application member. Often the sample applicationmember is comprised of a material that readily absorbs any of a varietyof fluid samples contemplated herein, and remains robust in physicalform. Frequently, the sample application member is comprised of amaterial such as white bonded polyester fiber. Moreover, the sampleapplication member, if present, is positioned in fluid-flow contact witha sample application pad.

In an embodiment, the label zone material may be treated with labeledsolution that includes material-blocking and label-stabilizing agents.Blocking agents include, for example, bovine serum albumin (BSA),methylated BSA, casein and nonfat dry milk. Stabilizing agents arereadily available and well known in the art, and may be used, forexample, to stabilize labeled reagents.

The label zone may contain a labeled reagent, often comprising one ormore labeled reagents. In many of the presently contemplatedembodiments, multiple types of labeled reagents are incorporated in thelabel zone such that they may permeate together with a fluid samplecontacted with the device. These multiple types of labeled reagent canbe analyte specific or control reagents and may have differentdetectable characteristics (e.g., different colors) such that onelabeled reagent can be differentiated from another labeled reagent ifutilized in the same device. As the labeled reagents are frequentlybound to a specific analyte of interest subsequent to fluid sample flowthrough the label zone, differential detection of labeled reagentshaving different specificities (including analyte specific and controllabeled reagents) may be a desirable attribute. However, frequently, theability to differentially detect the labeled reagents having differentspecificities based on the label component alone is not necessary due tothe presence of test and control zones in the device, which allow forthe accumulation of labeled reagent in designated zones.

The labeling zone may also include control-type reagents. These labeledcontrol reagents often comprise detectible moieties that will not becomerestrained in the test zones and that are carried through to the testregion and control zone(s) by fluid sample flow through the device. In afrequent embodiment, these detectible moieties are coupled to a memberof a specific binding pair to form a control conjugate which can then berestrained in a separate control zone of the test region by acorresponding member of the specific binding pair to verify that theflow of liquid is as expected. The visible moieties used in the labeledcontrol reagents may be the same or different color, or of the same ordifferent type, as those used in the analyte of interest specificlabeled reagents. If different colors are used, ease of observing theresults may be enhanced.

The test region may include a control zone for verification that thesample flow is as expected. Each of the control zones comprise aspatially distinct region that often includes an immobilized member of aspecific binding pair which reacts with a labeled control reagent. In anoccasional embodiment, the procedural control zone contains an authenticsample of the analyte of interest, or a fragment thereof. In thisembodiment, one type of labeled reagent can be utilized, wherein fluidsample transports the labeled reagent to the test and control zones; andthe labeled reagent not bound to an analyte of interest will then bindto the authentic sample of the analyte of interest positioned in thecontrol zone. In another embodiment, the control line contains antibodythat is specific for, or otherwise provides for the immobilization of,the labeled reagent. In operation, a labeled reagent is restrained ineach of the one or more control zones, even when any or all the analytesof interest are absent from the test sample.

Since the devices of the present disclosure may incorporate one or morecontrol zones, the labeled control reagent and their correspondingcontrol zones are preferably developed such that each control zone willbecome visible with a desired intensity for all control zones afterfluid sample is contacted with the device, regardless of the presence orabsence of one or more analytes of interest. In one embodiment, a singlelabeled control reagent will be captured by each of the control zones onthe test strip. Frequently, such a labeled control reagent will bedeposited onto or in the label zone in an amount exceeding the capacityof the total binding capacity of the combined control zones if multiplecontrol zones are present. Accordingly, the amount of capture reagentspecific for the control label can be deposited in an amount that allowsfor the generation of desired signal intensity in the one or morecontrol zones, and allows each of the control zones to restrain adesired amount of labeled control-reagent. At the completion of anassay, each of the control zones preferably provide a desired and/orpre-designed signal (in intensity and form).

In an embodiment, each control zone will be specific for a uniquecontrol reagent. In this embodiment, the label zone may include multipleand different labeled control reagents, equaling the number of controlzones in the assay, or a related variation. Wherein each of the labeledcontrol reagents may become restrained in one or more pre-determined andspecific control zone(s). These labeled control reagents can provide thesame detectible signal (e.g., be of the same color) or providedistinguishable detectible signals (e.g., have different colored labelsor other detection systems) upon accumulation in the control zone(s).

In an embodiment, the labeled control reagent comprises a detectiblemoiety coupled to a member of a specific binding pair. Typically, alabeled control reagent is chosen to be different from the reagent thatis recognized by the means which are capable of restraining an analyteof interest in the test zone. Further, the labeled control reagent isgenerally not specific for the analyte. In a frequent embodiment, thelabeled control reagent is capable of binding the corresponding memberof a specific binding pair or control capture partner that isimmobilized on or in the control zone. Thus the labeled control reagentis directly restrained in the control zone.

The use of a control zone is helpful in that appearance of a signal inthe control zone indicates the time at which the test result can beread, even for a negative result. Thus, when the expected signal appearsin the control line, the presence or absence of a signal in a test zonecan be noted.

Test zones of the present description include means that permit therestraint of an analyte of interest. Frequently, test zones of thepresent description include a ligand that is capable of specificallybinding to an analyte of interest. Alternatively, test zones of thepresent description include a ligand that is capable of specificallybinding the labeled reagent bound to an analyte of interest. Inpractice, a labeled test reagent binds an analyte of interest present ina fluid sample after contact of the sample with a representative deviceand flow of the fluid sample into and through the label zone.Thereafter, the fluid sample containing the labeled analyte progressesto a test zone and becomes restrained in the test zone. The accumulationof labeled analyte in the test zone produces a detectible signal.Devices may incorporate one or more test zones, each of which is capableof restraining different analytes, if present, in a fluid sample. Thus,in representative embodiments two, three, four, five or more (labeled)analytes of interest can be restrained in a single or different testzones, and thereby detected, in a single device.

The present devices may optionally further comprise an absorbent zonethat acts to absorb excess sample after the sample migrates through thetest region. The absorbent zone, when present lies in fluid flow contactwith the test region. This fluid flow contact can comprise anoverlapping, abutting or interlaced type of contact. In an occasionalembodiment, a control region (end of assay indicator) is provided in theabsorbent zone to indicate when the assay is complete. In thisembodiment, specialized reagents are utilized, such as pH sensitivereagents (such as bromocresol green), to indicate when the fluid samplehas permeated past all of the test and control zones.

As discussed above, the disclosed assay test reader may include one ormore sensors, such as the detector 104 illustrated in FIG. 1, whichoperate to determine whether a visual characteristic of an assayindicates the presence of an assay. The detectors may be any suitabletype of detector, such as a photo-detector including a PIN-diode baseddetector, a CCD sensor, a CMOS sensor, an InGaAs detector, or any othertype of photo-detector. Alternatively or in addition, the sensor may beconfigured to sense another characteristic of an assay test strip, suchas an electro-magnetic characteristic of the strip, a physicalcharacteristic of the strip (such as density or moisture retention), orany other suitable characteristic of the strip. These detectors may beincluded within the body of the disclosed assay test reader. In oneembodiment, the one or more detectors of the disclosed assay reader maybe affixed or connected to a body of the assay reader.

One or more light sources may be utilized in conjunction with the one ormore detectors such that during use, light from the light source orsources falls upon a portion of the porous carrier, such as the portion104 b of the assay strip 102 of FIG. 1, and is reflected or transmittedto the respective detector. For example, the light source may be anilluminator configured to generate light and to emit it in the directionof the portion 104 b of the assay test strip to be examined. Thedetector may then generate a current roughly proportional to the amountof light falling upon it. This current can be converted to a voltagesignal by a feeding it through a resistor, or a trans-impedanceamplifier, or by timed integration through a capacitor. The amount oflight reaching the detector may depend upon the amount of coloredparticulate label present and therefore the amount of analyte. In thisway, the amount of analyte present in the sample may be determined. Anexemplary method of optically determining the analyte concentrationusing one or more detectors is described more fully in EP 653625.

The disclosed detectors may include PIN-diode detectors as are wellknown in the art. In such PIN-diode detectors, photons entering thePIN-diode create a flow of current proportional to the amount of photonsreceived through the diode and into a resistor, a transimpedanceamplifier, or through a capacitor with time gating.. In the event that adetected photon creates or enables flow of current, the non-zero currentflowing through the diode causes a non-zero current, which is detectableby appropriate electronics coupled to the PIN-diode. For example,control electronics may be configured to receive signals from thedetector indicative of an amount of detected light, and may beconfigured to determine that such signals indicate a presence or anabsence of an analyte reaction as described in more detail below.

Alternatively or in addition, the disclosed detectors may includeimagers configured to generate similar signals indicative of a presenceor an absence of an analyte reaction. In such imagers, potentially alongwith a light source, detects the presence or absence of light at ananalyzed portion of the assay strip. The imager converts this detectedcolor into a digital signal (such as based on a magnitude of a generatedvoltage) and outputs that signal to appropriate electronics forhandling. For example, control electronics similar to those describedabove with respect to the PIN-diode based detector may convert aplurality of voltages into a signal indicative of a presence or anabsence of an analyte reaction.

It should be appreciated that a PIN-diode based detector may be lesscostly and more easily implemented than a CMOS-based imager.Specifically, the cost of the detector itself may be less for aPIN-diode based detector than for a CMOS-based imager, and the cost ofthe control or supporting electronics required to handle the signalsgenerated by the detector may also be lower for the PIN-diode baseddetector than for a CMOS-based imager. However, it should be appreciatedthat either type of detector (as well as any other type of knowndetector not explicitly discussed herein) is equally applicable in thecontext of the disclosed assay reader.

Any device which is compatible for detecting the presence of analytereactions (i.e., lines) on an assay test strip, such as a PIN detector,a CMOS imager, or another type of reflectance or fluorescence reader fordetermining the assay result is contemplated for use with the assayreader described herein. Certain suitable detector devices are known tothose of skill in the art (see, e.g., U.S. Pat. Nos. 5,658,801,5,656,502, 5,591,645, 5,500,375, 5,252,459, 5,132,097). Reflectance andother readers, including densitometers and transmittance readers, areknown to those of skill in the art (see, e.g., U.S. Pat. Nos. 5,598,007,5,132,097, 5,094,955, 4,267,261, 5,118,183, 5,661,563, 4,647,544,4,197,088, 4,666,309, 5,457,313, 3,905,767, 5,198,369, 4,400,353). Theuse of such detectors is achieved by mounting or otherwise affixing suchdetectors to the body of the assay reader, and enabling the test stripto move with respect to the body/detector combination, as describedabove.

Reference is now made to FIG. 2, which illustrates a plan view of anassay test strip reader as disclosed herein. Specifically, FIG. 2illustrates an assay test strip reader 200 including a body 202, anassay strip insertion portion 204, and a display 206.

In the illustrated embodiment, an assay test strip 102 is encased in ahousing, casing, or shell 208. That is, the illustrated assay test strip102 is contained within the shell 208 to form a cartridge insertable inthe reader. In one embodiment, the housing 208 is a plastic shellconfigured to protect the assay strip 102 from accidental contaminationand damage, and configured to prevent biological fluid on the strip 102from entering the body 202 of the assay test strip reader or fromtouching the skin of a user of the reader 200. The housing mayalternatively be made another inert material, other than plastic, thatdoes not interfere with the assay procedure.

In the illustrated embodiment, an assay test strip 102, similar to theassay test strip 102 of FIG. 1, is illustrated as encased in a housing208, which housing is partially inserted in the reader 200. Theinsertion portion 204 of the body 202 is sized to receive the housing208 of the assay test strip 102, such as by being slightly larger thanthe cross section of housing 208 of the assay test strip 102.

It should be appreciated that the disclosed assay reader 200 may beconfigured to receive an assay strip 102 which is not encased in ahousing such as housing 208. In such an embodiment embodiment, the assaystrip insertion portion 204 is sized to receive the assay strip 102without any housing.

The amount of the test strip 102 which is visible through the housing orshell 208 may vary based, for example, on a quantity of antibody regionsor portions on the strip. The housing 208 may be made from any suitablematerial, including plastic or other suitable material. Further, thehousing 208/test strip 102 assembly may be reusable, such as byreplacing the test strip 102 within the housing 208. Alternatively, thehousing 208/test strip 102 assembly may be disposable, wherein theentire assembly is disposed after use.

In the illustrated embodiment, the detector included within the body 202of the assay test strip reader 200 is not visible, and thus is notshown. In one embodiment, light from an illuminator or other lightsource contained within the body 200 may be visible exiting theinsertion portion 204. This light may enable the detector to obtain anaccurate reading of the lines, such as line 106 c, that are visible onthe assay test strip 102 following application of biological fluid.

The assay reader disclosed herein may be configured to operate with anyof the different assay test strips described above. Moreover, inembodiments wherein a housing 208 is included for use with an assay teststrip, an appropriate housing or shell may be provided which can operatewith any of the different types of assay test strips described above. Inan embodiment, the disclosed reader operates with another diagnostictool other than an assay test strip. That is, any diagnostic mediumwhich could indicate the presence or absence of a diagnostic conditionmay be inserted into the body of the disclosed reader, and the sensorcontained in the disclosed reader may be utilized to detect the presenceor absence of the diagnostic condition.

The disclosed assay reader utilizes at least one detector, positionedwithin the body of the reader, to determine the condition of an assaytest strip following an appropriate analyte-reaction test. Specifically,by affixing the detector to the body, the disclosed reader relies on themotion of the test strip relative to the body/detector combination toenable the detector to accurately detect the results of the test. Forexample, if a single detector us used, it is fixedly attached to thebody such that the detector can detect the optical condition of the teststrip.

A test strip may be inserted or removed from within the body, such thatthe test strip moves relative to both the body and the detector. In anembodiment wherein a single detector is utilized, the motion of the teststrip into and out of the body causes the detector to scan a linear(i.e., a one-dimensional) portion of the test strip. As the test stripis scanned, a one-dimensional profile of the test strip is created, theprofile including a representation of the various opticalcharacteristics of the strip. In an embodiment, the disclosed readerstores (e.g., in the control electronics) data representative of theone-dimensional profile of the test strip.

FIG. 3 is an image of an example assay test strip 300 in which two testlines 302 and 304 are present. Specifically, FIG. 3 is a two-dimensionalimage of an assay test strip 300 indicating both the length and thewidth of the assay test strip 300, and also indicating where on theassay test strip the two analyte reaction regions (i.e., the two testlines 302 and 304) are positioned. In the illustrated embodiment, thetwo test lines 302 and 304 are indicated by a darker color of the assaytest strip at the portion of the strip containing the two test lines.

FIG. 4 illustrates an example one-dimensional representation of aprofile of a test strip 400, such as the test strip 300 illustrated inFIG. 3, inserted in the an embodiment of the disclosed reader. In theillustrated embodiment, the vertical axis 402 of FIG. 4 represents thestrength of a signal generated by a detector or sensor of the disclosedreader. The horizontal axis 404 of FIG. 4 represents the position of theinserted test strip (such as test strip 300) that corresponds with thedetected signal. In the illustrated embodiment, the test strip insertedin the disclosed reader indicates an analyte reaction at a positioncorresponding to slightly more than the “100” position of the horizontalaxis, indicated by numeral 410, and also indicates an analyte reactionat a position slightly less than the “250” position of the horizontalaxis, indicated by numeral 420. It should be appreciated that theanalyte reactions illustrated in FIG. 3 are represented in FIG. 4 by therelatively high signal generated at these two positions 302 and 304 ofthe assay test strip 300 discussed above. Thus, it should be appreciatedthat the positions 302 and 304 of the test lines of FIG. 3 maycorrespond to the position 410 which is slightly more than “100” of FIG.4, and to the position 420 which is slightly less than “250” of FIG. 4.

In an embodiment, the control electronics of the disclosed reader storedata indicative of the detected profile. For example, the controlelectronics of the disclosed reader may store data indicative of theprofile illustrated in FIG. 4. This data may be stored in anyappropriate way as is well known in the art, such as by storing aplurality or ordered pairs representing an x-coordinate (e.g., aposition on the assay strip) and a y-coordinate (e.g., a valueindicative of a magnitude of a detected signal). Based on the createdprofile, control electronics coupled to the detector may determine atleast one outcome (or data indicative of an outcome) of the test, suchas by determining that the test resulted in a “positive” or “negative”result. For example, this determination may be made based on thoseportions of the profile which reflect relative signals, and thusindicate that a line is present on the scanned assay test strip.

In various embodiments, the control electronics disclosed herein receivesignals from any sensor(s) disposed within the body of the reader, whichare proportional to an amount of a measured characteristic. For example,if a measured characteristic of the reader is the color of a line on anassay test strip, the sensor may output a signal proportional to theintensity of such color. Likewise, if a measured characteristic of thereader is a magnetic field induced by the test strip, the sensor mayoutput a signal proportional to the strength of the magnetic field. Thisproportional signal may enable the control electronics to discern aresult of the test based, at least in part, on an amount of a detectedsignal (i.e., as opposed to merely the presence of a detected signal.

In an embodiment, the disclosed reader is configured to make aqualitative determination about the outcome of a test (e.g., at“positive” or “negative” outcome) based on the existence of a signalsensed by a sensor. In another embodiment, the disclosed reader isconfigured to make a quantitative determination (e.g., a determinationas to an analyte concentration within a sample) which is useful indetermining a condition of the provider of the sample. For example, aquantitative determination as to the blood-glucose concentration of asubject may be made by the disclosed reader based on a magnitude of asignal generated by a sensor.

The control electronics of the disclosed assay strip reader may be awareof the pattern of antibody regions on an inserted assay test strip inorder to determine a qualitative result of a test. For example, thecontrol electronics may be aware that it should expect the detection oftwo or three different lines depending on a particular result of thetest. Moreover, the control electronics may be aware, roughly, of theposition of the expected lines within the assay test strip. For example,the control electronics may expect a first line, recognize that a secondline may or may not be detected, and expect a third line, wherein thesecond line is approximately halfway between the first line and thethird line. In this embodiment, the control electronics may verify thecorrectness of the functioning of the test by ensuring that if only twolines are present, the amount of space between the two lines is roughlytwice the amount of space between each of three expected lines. In anembodiment, the assay test reader determines that it is functioningproperly simply by counting the number of detected lines and whitespaces between lines to ensure that the proper reactions have occurredgiven the particular type of test being performed.

This awareness in the control electronics may be pre-programmed into thecontrol electronics, such that particular control electronics areconfigured to detect results of particular tests. Alternatively, thecontrol electronics of an assay test reader as disclosed herein may beprogrammable, such as by connecting the assay reader device to acomputerized device so as to enable the computerized device to uploadinstructions to the assay test strip reader.

In an embodiment, the control electronics are unaware about the type ofprofile to expect when scanning an assay test strip. For example, thecontrol electronics may simply receive data indicative of aone-dimensional profile, and may either output the raw data directly toa display device, or may upload that data to a remote computer devicefor handling. Thus, in these embodiments, the control electronics mayonly need to be able to handle raw profile data, such as by outputtingthe raw data or by uploading the raw data to a remote computing device.

The optical signals measured by the detector may be reflectance orfluorescent signals. As discussed above, the detector may be anysuitable type of detector, such as a PIN-diode based detector, a CMOSimager, or another type of detector. The detector may include or beassociated with an illuminator or other light source to enable thedetector to accurately read the assay test strip inserted in the assayreader. The detector may be oriented so as to directly face a testsurface of the test strip, or may be oriented to detect opticalcharacteristics of the assay test strip based on one or more reflectionsof the surface of the test strip. The detector may be powered by anon-board battery or may be powered based on an always-on power source,such as power from a standard wall outlet. The detector may provide rawsignals, such as a voltages, directly to the associated electronics,further amplify or filter these signals, or may convert these signals todigital data indicative of the detected optical properties of the teststrip and thereafter provide that digital data to the associatedelectronics for further processing.

The detector as described herein may include a plurality of detectors,such as a plurality of detectors arranged as an array of detectors. Insuch an embodiment, each of the plurality of detectors maysimultaneously determine optical data about the test strip, such thatfor each position of the test strip during insertion and/or removal fromthe body, a plurality of different data points are collected. It shouldbe appreciated that with such an array of detectors, the disclosedreader may enable the creation of data indicative of a two-dimensionalportion of the test strip. The width of this two-dimensional portion maybe based on the width of the array of detectors, and the length of thistwo-dimensional portion may be based on the distance the test strip isslid or otherwise moved with respect to the detector within the body.

In one embodiment, the reader disclosed herein creates a two-dimensionalimage by creating a plurality of images (whether one-dimensional imagesor two-dimensional images) in a time-lapse fashion, and by thereafterstacking, stitching, or otherwise combining the images on top of oneanother. In this stitching environment, the disclosed system may enableaccurate recreation of distances within the test strip, such as bycalculating the appropriate location for each stacked or stitched imagebased on a known width of the strip, length of movement of the strip,and/or delay between time-lapsed image captures.

The disclosed assay reader may include one or more display devicesconfigured to display information about the scanned test strip to a userof the reader. For example, one or more LCD, LED, or other type ofelectronic display devices may be connected to the electronics and/orthe detector to display information indicative of an outcome of the scanof the test strip. This information may include an outcome of a test(such as a “positive” or “negative” outcome), a number indicative of acharacteristic of biological fluid tested (such as an amount orconcentration of a particular substance in the fluid), or other dataindicative of a characteristic of the assay strip.

In one embodiment, the display device is a device configured to output avisual indication of a result of a test. For example, the display devicecould be the LCD, LED, or other type of electronic display devicediscussed above. In another embodiment, the display device is a devicewhich non-electronically displays an indication of a result of a test.For example, the display device may include a substrate configured tochange colors depending on the characteristics of the assay test stripdetected by the one or more sensors within the body of the disclosedreader.

In one embodiment, the disclosed display device may include an audiooutput device configured to output an audio signal indicative of aresult of a test. For example, the display device may be configured toemit an audible tone if a designated result of the test is achieved—suchas if a test results in a “positive” outcome. If the disclosed reader isconfigured to make a quantitative determination of the outcome of thetest, the audible tone may vary in intensity, length, pitch, or anothercharacteristic to indicate the quantitative determination regarding theoutcome of the test. These audible tones may include synthesized speechconfigured to generate the sound of words understandable by an operatorof the disclosed reader.

In a further embodiment, the assay reader is connectable to an existingcomputing device separate from the assay reader itself, such as apersonal computer, via a wired (e.g., USB, serial, or other wiredtechnology) or wireless (e.g., WiFi, Bluetooth, or other wirelesstechnology) connection. In this embodiment, data about the state of theassay strip may be uploaded from the reader to the separate computingdevice. Upon such uploading, the separate computing device may performadditional processing on the data, may store the data, may send the datato a third party such as a health care professional or other health careentity, or may otherwise handle or analyze the data. In this embodiment,the reader itself may not include a display; rather, the display deviceof the personal computer may be relied on to display the detectedinformation. In various embodiments, the separate computing device towhich the reader connects may include a special-purpose electronicdevice, a personal digital assistant (“PDA”), a cellular telephone, alaptop computer, a tablet computer, an interactive television systemincluding a set-top box, or any other appropriate type ofmicroprocessor-based device.

The disclosed reader utilizes the motion of the test strip relative tothe body/detector assembly to form or construct the profile of theanalyte regions on the test strip. That is, the disclosed readerovercomes certain of the drawbacks of prior art readers by fixing thelocation of the detector with respect to the body, and by determining aone- or two-dimensional profile of the assay strip based on movement ofthe assay strip itself with respect to the detector. This motion mayoccur with the insertion and/or removal of the assay strip from the bodyof the reader, such as with the insertion and removal by a user oroperator of the reader.

Alternatively, insertion of the test strip by a user may load a springmechanism within the body of the reader. Release of the spring mechanismmay push the test strip out of the body of the reader, and the detectormay scan the strip as it is pushed out of the body of the reader.Release of the spring mechanism may be achieved by a mechanical devicesuch as a switch, or by an opto-electronic device such as anelectronically-triggered switch controlled by the electronics of thereader. For instance, upon the electronics confirming that the teststrip is properly inserted in the reader, the electronics may trigger aswitch to release the spring mechanism, ejecting the test strip andenabling the detector to scan the analyte profile of the test strip.

In one embodiment, the relative position of the lines representingreactions of analytes in a biological fluid with a substance disposed onthe assay test strip is important to the outcome of a particular test.For example, if three different regions are present on a test strip, itmay not be enough to simply know that two of the regions reacted withanalytes in the sample to form visible lines. Rather, it may beimportant to know which of the two lines are visible, and thus which ofthe two lines reacted with analytes in the sample. Such determinationsmay be made based on the relative positions of each of the lines to oneanother. In an embodiment, an analyte test strip (or a cartridge intowhich such a strip is inserted) may include an encoder usable by thecontrol electronics to determine the relative position of the strip (orthe cartridge) with respect to the detector at a given point in time.

For example, an encoder may include a plurality of printed marks on thetest strip (or the cartridge) which are read by a detector, such as oneof the detectors in an array of detectors included in the disclosedreader. The control electronics may utilize the detected printed marksto determine the position of the test strip within the body at a pointin time. For example, a test strip (or cartridge) may include an encoderhaving markings every three millimeters along the length of thecartridge. By sensing these markings with a detector in the reader, thedisclosed control electronics may be able to distinguish between avisible line at a first region (such as at a region at a “zero”position) and a visible line at a second region (such as a region sixmillimeters beyond the “zero” position). The ability to so distinguishbetween the relative positions of the analyte regions may enable thereading of more complex tests to be automated in a simple, affordable,portable device.

In such an embodiment, wherein an encoder is included, the disclosedreader may also be able to determine the visible widths of variousanalyte regions (either relative to one another or absolutely) based onthe detection of various markings of the encoder. Thus, for tests whoseresults depend upon the relative widths of the various analyte regions,the disclosed reader can provide accurate analysis of the results of thetests while minimizing the potential for human error.

The disclosed encoder may also enable the disclosed reader to accuratelydetermine whether a signal is present at a designated location on anassay test strip. For example, if a designated region of the assay teststrip is configured to indicate the presence or absence of an analyte ina sample, the encoder may enable the reader to determine when a detectoris analyzing that designated region of the assay test strip. If, basedon the encoder, the disclosed reader determines that the detector isanalyzing the designated region, the reader may determine with certaintywhether the designated region of the assay test strip reacted with thesample, and thus whether the tested-for analyte is present. Thus, thedisclosed encoder can enable the reader to determine whether adesignated portion of the assay test strip is being analyzed by thedetector.

Alternatively or in addition, the disclosed reader may utilize anencoder such as described above to linearize the motion of the assaytest strip within the reader. For example, the encoder may enable thecontrol electronics, which are coupled to the detector, to construct anaccurate representation of the color properties of the assay test strip,including an accurate representation of the spacing of the detectedregions, by utilizing the encoder to linearize the results. For example,if an encoder includes a mark every two millimeters, the disclosedreader may rely on those marks to construct a representation of theanalyte reaction regions of the test strip regardless of the speed withwhich the test strip was passed through the reader. Even if the firstfour millimeters of a test strip are inserted and/or removed morequickly or more slowly than the remainder of the test strip, the controlelectronics can utilize the detected encoder marks to construct anaccurate representation of the colors on the test strip.

In an embodiment, an encoder such as the encoder described herein can beutilized to identify the test strip from among a plurality of differenttest strips. For example, the disclosed encoder could be disposed on thetest strip as a barcode which identifies the type of test enabled by thestrip, the name of the individual whose sample is applied to the teststrip, information required to calibrate the test strip, assay lotinformation, or other suitable information about the particular testimplemented by the test strip. Alternatively, the encoder may covey suchinformation without being displayed as a bar code—that is, theinformation may be conveyed in some other suitable way based on thedetected marks of the encoder disposed on the assay test strip. Itshould be appreciated that any suitable information may be conveyed bythe encoder, and any suitable use of that information may be made by thedisclosed reader.

In an embodiment, the disclosed reader is configured to detect the colorproperties of an inserted assay strip upon the strip being inserted,removed, or both inserted and removed. For example, if the disclosedreader is configured to detect the characteristics of an assay teststrip upon both insertion and removal, the control electronics mayutilize the insertion or the removal as an error-checking mechanism toensure that the same information is detected upon both insertion andremoval. Alternatively the disclosed reader may utilize the datadetected upon insertion and removal to construct a stronger profile ofthe assay strip, or to construct a profile of the assay test strip whichcontains more data, making the profile more accurate and/or morereliable.

In an embodiment, such as the embodiments discussed above, the encoderdisclosed herein is configured to be detected by an optical detector,such as a PIN-diode. In another embodiment, the encoder is not opticallydetectable, but rather is detectable using some other type of detectionmechanism. For example, the disclosed encoder may be electricallydetectable, electromagnetically or may be detectable based on anelectromagnetic emission of the encoder. In another embodiment, thedisclosed encoder relies on one or more potentiometers to determine theposition of the assay test strip within the body of the reader. Forexample, one or more linear or rotary potentiometers is positionedwithin the body of the reader, such that upon an assay test strip beinginserted in the reader, the assay test strip engages the potentiometer.Upon engaging the potentiometer, the assay test strip displaces at leastone element of the potentiometer during insertion and/or removal of thetest strip from the body of the reader. During insertion and/or removal,the engaging element of the potentiometer is displaced proportionatelyto the amount of displacement of the assay test strip within the body ofthe reader. The potentiometer detects the amount of displacement, whichdetected amount of displacement can be utilized by the controlelectronics to determine the position of the assay test strip within thebody of the reader. Thus, it should be appreciated that a potentiometer,arranged as described, can function as an electro-mechanical encoder andcan enable the disclosed reader to ascertain the position of the teststrip within the reader during insertion and removal of the test strip.

In an embodiment, the reader disclosed herein includes an on/off switchor another manually actuatable mechanism by which the reader is turnedon and/or off. In another embodiment, the disclosed reader is turned onupon the insertion of the test strip into the reader. For example, thedisclosed reader may be configured to be powered off, or placed in alow-power state, until and unless a test strip is inserted in the bodyof the reader. Upon insertion of the test strip in the body of thereader, the reader may be powered on for use. In an embodiment, thereader is powered off, or placed in a low-power state, upon the teststrip being removed from the reader. In another embodiment, the readerremains powered on for a designated amount of time after the detectionof the color properties of the strip, such as to enable a user to readthe display device and any indication of the results of the testcontained thereon. In summary, the disclosed assay test strip readeranalyzes the optical properties of an assay test strip, after that teststrip has been utilized to conduct an analyte detection test, todetermine the results of the test. The strip is inserted into the bodyof the reader, and the motion of the strip relative to one or moredetectors connected to (and immovable with respect to) the body of thereader enables the disclosed system to create a one- or two-dimensionalprofile of the test strip. Control electronics coupled to the detectormay analyze the profile and provide feedback to a user of the assaystrip reader. This low cost alternative to expensive, motorized scanningdevices enables a reader which can accurately detect a plurality ofanalyte regions on a test strip and can therefore accurately output dataindicative of the outcome of the test.

In an embodiment, the disclosed reader is not configured to have theassay strip inserted into a body of the reader. In this embodiment, oneor more sensors or detectors are configured to detect characteristics ofan assay strip without the assay strip being inserted into the body ofthe reader based on the relative motion of the assay strip with respectto the reader. For example, the disclosed reader may be movable by ahuman operator over an assay test strip, such as would be done with ascanning wand. Alternatively, the disclosed reader may be stationary,and a human operator may move the assay strip over the reader, such asis done when scanning a bar-code at a supermarket checkout station.Thus, it should be appreciated that in various embodiments, the assaytest strip is not insertable in the body of the reader, but the readeris nonetheless configured to scan the assay test strip to determine anyreactions which have occurred on the assay test strip.

It should be understood by those skilled in the art that variousmodifications, combinations, sub-combinations and alterations may occurdepending on design requirements and other factors insofar as they arewithin the scope of the appended claims or the equivalents thereof.

What we claim is:
 1. A method of analyzing an assay test stripcomprising a test portion and an encoder portion, the method comprising:moving, by a user, the assay test strip relative to a body of an assaytest strip reader; and detecting a presence of at least one analytereaction region based on at least one characteristic of the at least oneanalyte reaction region during the user-caused moving of the assay teststrip relative to the body of the assay test strip reader, wherein thedetection takes place during the user-caused moving of the assay teststrip relative to the body of the assay reader